Effects of Transient Receptor Potential Cation 5 (TRPC5) Inhibitor, NU6027, on Hippocampal Neuronal Death after Traumatic Brain Injury
Traumatic brain injury (TBI) can cause physical, cognitive, social, and behavioral changes that can lead to permanent disability or death. After primary brain injury, translocated free zinc can accumulate in neurons and lead to secondary events such as oxidative stress, inflammation, edema, swelling...
| Main Authors: | , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2020-11-01
|
| Series: | International Journal of Molecular Sciences |
| Subjects: | |
| Online Access: | https://www.mdpi.com/1422-0067/21/21/8256 |
| _version_ | 1797548897082540032 |
|---|---|
| author | Min Kyu Park Bo Young Choi A Ra Kho Song Hee Lee Dae Ki Hong Jeong Hyun Jeong Dong Hyeon Kang Beom Seok Kang Sang Won Suh |
| author_facet | Min Kyu Park Bo Young Choi A Ra Kho Song Hee Lee Dae Ki Hong Jeong Hyun Jeong Dong Hyeon Kang Beom Seok Kang Sang Won Suh |
| author_sort | Min Kyu Park |
| collection | DOAJ |
| description | Traumatic brain injury (TBI) can cause physical, cognitive, social, and behavioral changes that can lead to permanent disability or death. After primary brain injury, translocated free zinc can accumulate in neurons and lead to secondary events such as oxidative stress, inflammation, edema, swelling, and cognitive impairment. Under pathological conditions, such as ischemia and TBI, excessive zinc release, and accumulation occurs in neurons. Based on previous research, it hypothesized that calcium as well as zinc would be influx into the TRPC5 channel. Therefore, we hypothesized that the suppression of TRPC5 would prevent neuronal cell death by reducing the influx of zinc and calcium. To test our hypothesis, we used a TBI animal model. After the TBI, we immediately injected NU6027 (1 mg/kg, intraperitoneal), TRPC5 inhibitor, and then sacrificed animals 24 h later. We conducted Fluoro-Jade B (FJB) staining to confirm the presence of degenerating neurons in the hippocampal cornus ammonis 3 (CA3). After the TBI, the degenerating neuronal cell count was decreased in the NU6027-treated group compared with the vehicle-treated group. Our findings suggest that the suppression of TRPC5 can open a new therapeutic window for a reduction of the neuronal death that may occur after TBI. |
| first_indexed | 2024-03-10T15:06:22Z |
| format | Article |
| id | doaj.art-aa1aa03532024ab9923b3e25df0e41dc |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-10T15:06:22Z |
| publishDate | 2020-11-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-aa1aa03532024ab9923b3e25df0e41dc2023-11-20T19:45:13ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672020-11-012121825610.3390/ijms21218256Effects of Transient Receptor Potential Cation 5 (TRPC5) Inhibitor, NU6027, on Hippocampal Neuronal Death after Traumatic Brain InjuryMin Kyu Park0Bo Young Choi1A Ra Kho2Song Hee Lee3Dae Ki Hong4Jeong Hyun Jeong5Dong Hyeon Kang6Beom Seok Kang7Sang Won Suh8Department of Physiology, College of Medicine, Hallym University, Chuncheon 24252, KoreaDepartment of Physiology, College of Medicine, Hallym University, Chuncheon 24252, KoreaDepartment of Physiology, College of Medicine, Hallym University, Chuncheon 24252, KoreaDepartment of Physiology, College of Medicine, Hallym University, Chuncheon 24252, KoreaDepartment of Physiology, College of Medicine, Hallym University, Chuncheon 24252, KoreaDepartment of Physiology, College of Medicine, Hallym University, Chuncheon 24252, KoreaDepartment of Medical science, College of Medicine, Hallym University, Chuncheon 24252, Kangwon-Do, KoreaDepartment of Physiology, College of Medicine, Hallym University, Chuncheon 24252, KoreaDepartment of Physiology, College of Medicine, Hallym University, Chuncheon 24252, KoreaTraumatic brain injury (TBI) can cause physical, cognitive, social, and behavioral changes that can lead to permanent disability or death. After primary brain injury, translocated free zinc can accumulate in neurons and lead to secondary events such as oxidative stress, inflammation, edema, swelling, and cognitive impairment. Under pathological conditions, such as ischemia and TBI, excessive zinc release, and accumulation occurs in neurons. Based on previous research, it hypothesized that calcium as well as zinc would be influx into the TRPC5 channel. Therefore, we hypothesized that the suppression of TRPC5 would prevent neuronal cell death by reducing the influx of zinc and calcium. To test our hypothesis, we used a TBI animal model. After the TBI, we immediately injected NU6027 (1 mg/kg, intraperitoneal), TRPC5 inhibitor, and then sacrificed animals 24 h later. We conducted Fluoro-Jade B (FJB) staining to confirm the presence of degenerating neurons in the hippocampal cornus ammonis 3 (CA3). After the TBI, the degenerating neuronal cell count was decreased in the NU6027-treated group compared with the vehicle-treated group. Our findings suggest that the suppression of TRPC5 can open a new therapeutic window for a reduction of the neuronal death that may occur after TBI.https://www.mdpi.com/1422-0067/21/21/8256traumatic brain injuryzincNU6027transient receptor potential cation channel 5neuronal death |
| spellingShingle | Min Kyu Park Bo Young Choi A Ra Kho Song Hee Lee Dae Ki Hong Jeong Hyun Jeong Dong Hyeon Kang Beom Seok Kang Sang Won Suh Effects of Transient Receptor Potential Cation 5 (TRPC5) Inhibitor, NU6027, on Hippocampal Neuronal Death after Traumatic Brain Injury International Journal of Molecular Sciences traumatic brain injury zinc NU6027 transient receptor potential cation channel 5 neuronal death |
| title | Effects of Transient Receptor Potential Cation 5 (TRPC5) Inhibitor, NU6027, on Hippocampal Neuronal Death after Traumatic Brain Injury |
| title_full | Effects of Transient Receptor Potential Cation 5 (TRPC5) Inhibitor, NU6027, on Hippocampal Neuronal Death after Traumatic Brain Injury |
| title_fullStr | Effects of Transient Receptor Potential Cation 5 (TRPC5) Inhibitor, NU6027, on Hippocampal Neuronal Death after Traumatic Brain Injury |
| title_full_unstemmed | Effects of Transient Receptor Potential Cation 5 (TRPC5) Inhibitor, NU6027, on Hippocampal Neuronal Death after Traumatic Brain Injury |
| title_short | Effects of Transient Receptor Potential Cation 5 (TRPC5) Inhibitor, NU6027, on Hippocampal Neuronal Death after Traumatic Brain Injury |
| title_sort | effects of transient receptor potential cation 5 trpc5 inhibitor nu6027 on hippocampal neuronal death after traumatic brain injury |
| topic | traumatic brain injury zinc NU6027 transient receptor potential cation channel 5 neuronal death |
| url | https://www.mdpi.com/1422-0067/21/21/8256 |
| work_keys_str_mv | AT minkyupark effectsoftransientreceptorpotentialcation5trpc5inhibitornu6027onhippocampalneuronaldeathaftertraumaticbraininjury AT boyoungchoi effectsoftransientreceptorpotentialcation5trpc5inhibitornu6027onhippocampalneuronaldeathaftertraumaticbraininjury AT arakho effectsoftransientreceptorpotentialcation5trpc5inhibitornu6027onhippocampalneuronaldeathaftertraumaticbraininjury AT songheelee effectsoftransientreceptorpotentialcation5trpc5inhibitornu6027onhippocampalneuronaldeathaftertraumaticbraininjury AT daekihong effectsoftransientreceptorpotentialcation5trpc5inhibitornu6027onhippocampalneuronaldeathaftertraumaticbraininjury AT jeonghyunjeong effectsoftransientreceptorpotentialcation5trpc5inhibitornu6027onhippocampalneuronaldeathaftertraumaticbraininjury AT donghyeonkang effectsoftransientreceptorpotentialcation5trpc5inhibitornu6027onhippocampalneuronaldeathaftertraumaticbraininjury AT beomseokkang effectsoftransientreceptorpotentialcation5trpc5inhibitornu6027onhippocampalneuronaldeathaftertraumaticbraininjury AT sangwonsuh effectsoftransientreceptorpotentialcation5trpc5inhibitornu6027onhippocampalneuronaldeathaftertraumaticbraininjury |